Neanderthal Gene Variants Linked to Increased Pain Sensitivity

Published in Communications Biology, these results represent the most recent evidence of how interactions with Neanderthals in the past have left a genetic impact on the makeup of contemporary humans.

In their study, the researchers identified that individuals harboring three specific Neanderthal gene variants within SCN9A, a gene associated with sensory neurons, exhibit increased sensitivity to pain when subjected to skin pricking after prior exposure to mustard oil.

Prior investigations had uncovered three SCN9A gene variations (M932L, V991L, and D1908G) within sequenced Neanderthal genomes. Reports had also suggested heightened pain sensitivity in individuals carrying all three variants. Nevertheless, the precise sensory responses influenced by these genetic variations remained uncertain until this study.

An international consortium, spearheaded by scientists at UCL, Aix-Marseille University, University of Toulouse, Open University, Fudan University, and Oxford University, and with financial support from Wellcome, assessed the pain thresholds of 1,963 individuals in Colombia. They gauged these thresholds by exposing participants to a variety of stimuli.

The SCN9A gene governs a sodium channel primarily active in sensory neurons responsible for detecting signals related to tissue damage. In the studied population, the D1908G variant of this gene was identified in approximately 20% of the chromosomes. Notably, about 30% of the chromosomes with the D1908G variant also contained the M932L and V991L variants.

The study revealed that the presence of the three Neanderthal gene variants resulted in lower pain thresholds in response to skin pricking following exposure to mustard oil. However, this heightened sensitivity to pain was not observed in response to heat or pressure. Furthermore, individuals carrying all three of these variants displayed even greater pain sensitivity compared to those with just one of the variants.

Upon scrutinizing the genomic region encompassing SCN9A with genetic data from 5,971 individuals hailing from Brazil, Chile, Colombia, Mexico, and Peru, the researchers observed a higher prevalence of the three Neanderthal variants in populations with increased Native American ancestry. For instance, in the Peruvian population with an average Native American ancestry proportion of 66%, these variants were notably more frequent.

The researchers suggest that these Neanderthal variants could potentially heighten the sensitivity of sensory neurons by modifying the threshold for generating nerve impulses. They speculate that these variants’ prevalence in populations with significant Native American ancestry might be attributed to random chance and population bottlenecks during the early peopling of the Americas. While acute pain can shape behavior and prevent further injury, scientists emphasize the necessity for further research to ascertain if carrying these variants and experiencing heightened pain sensitivity might have conferred evolutionary advantages in human history.

Prior investigations led by co-corresponding author Dr. Kaustubh Adhikari (Affiliated with UCL Genetics, Evolution & Environment and The Open University) have revealed that Neanderthal genetic contributions have influenced the morphology of human noses.*

In the last 15 years, since the Neanderthal genome was first sequenced, we have been learning more and more about what we have inherited from them as a result of interbreeding tens of thousands of years ago.

“Pain sensitivity is an important survival trait that enables us to avoid painful things that could cause us serious harm. Our findings suggest that Neanderthals may have been more sensitive to certain types of pain, but further research is needed for us to understand why that is the case, and whether these specific genetic variants were evolutionarily advantageous.

Kaustubh Adhikari
UCL Genetics, Evolution & Environment and The Open University

We have shown how variation in our genetic code can alter how we perceive pain, including genes that modern humans acquired from the Neanderthals. But genes are just one of many factors, including environment, past experience, and psychological factors, which influence pain.

Pierre Faux
Aix-Marseille University and University of Toulouse

Resources

1. ^NEWSPAPER UCL News. (2023, October 10). Neanderthal gene variants associated with greater pain sensitivity. UCL News. [UCL News]
2. ^JOURNAL Faux, P., Li, D., Ramírez, L. S., Chacón-Duque, J. C., Comini, M., Mendoza‐Revilla, J., Fuentes-Guajardo, M., Jaramillo, C., Arias, W., Hurtado, M., Villegas, V., Granja, V., Barquera, R., Everardo-Martínez, P., Quinto-Sánchez, M., Gómez-Valdés, J., Villamil‐Ramírez, H., De Cerqueira, C. C. S., Hünemeier, T., . . . Ruiz-Linares, A. (2023). Neanderthal introgression in SCN9A impacts mechanical pain sensitivity. Communications Biology, 6(1). [Communications Biology]